Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine

Fan, Yao-Chung; Chen, Jo Mei; Lin, Jen Wei; Chen, Yiying; Wu, G.; Su, Kuan Hsuan; Chiou, Ming Tang; Wu, Shang; Yin, Ji Hang; Liao, Jiunn‐Wang; Chang, Gwong Jen J.; Chiou, Shyan Song

doi:10.1038/s41598-018-25596-1

Cited by 17 publications

(24 citation statements)

References 58 publications

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“…These results were consistent with a previous observation that GI virus-like particles failed to cross-protect 10% of vaccinated mice against GIII viral challenge [29]. However, swine immunized with these GI virus-like particles showed no fever, viremia or viral RNA in tissues after GI or GIII viral challenge, demonstrating sterile protection against GI and GIII viral infection in swine [29]. Therefore, more detailed studies are needed to evaluate the cross-protective efficacy of GI-derived vaccines against GIII viral infection.…”

Section: Discussionsupporting

confidence: 93%

“…Given the emergence of the GI virus as the dominant genotype in Asian regions and the partial cross-protection efficacy of GIII-derived vaccines against GI viral infection, development of a GI-derived vaccine has been proposed to control GI viral infection [25,28,29]. We therefore examined the protective efficacy of a GI-derived vaccine against the challenge of GI and GIII viruses.…”

Section: Resultsmentioning

confidence: 99%

“…These epidemiological data together with the reduced protective efficacy of GIII-derived vaccines against GI virus infection suggest a potential need for a GI-derived vaccine. In fact, several trials for the development of a GI-derived vaccine have been reported [25,28,29].…”

Section: Discussionmentioning

confidence: 99%

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Partial cross-protection between Japanese encephalitis virus genotype I and III in mice

et al. 2019

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Genotype III (GIII) Japanese encephalitis virus (JEV) predominance has gradually been replaced by genotype I (GI) over the last 20 years in many Asian countries. This genotype shift raises concerns about the protective efficacy of Japanese encephalitis (JE) vaccines, as all of the currently licensed JE vaccines are derived from GIII strains. In this study, we conducted vaccination-challenge protection assays to evaluate the cross-protective efficacy of GI- or GIII-derived vaccines against the challenge of a heterologous genotype using a mouse challenge model. Titration of the neutralizing antibodies elicited by SA14-14-2 live-attenuated JE vaccine (SA14-14-2 vaccine), a GIII-derived vaccine, indicated that the titer of neutralizing antibodies specific to heterologous genotype GI stain was significantly lower than that specific to homologous genotype GIII strain in both pigs and mice immunized with the SA14-14-2 vaccine. Vaccination of mice with SA14-14-2 vaccine or a GIII-inactivated vaccine at high and medium doses completely protected vaccinated mice against challenge with the homologous genotype GIII strains, but failed to provide the vaccinated mice complete protection against the challenge of heterologous genotype GI strains. The protection rates against GI strain challenge were 60%–80%, showing that these vaccines were partially protective against GI strain challenge. Additionally, vaccination of mice with a GI-inactivated vaccine conferred 100% protection against the challenge of homologous genotype GI strains, but 50%–90% protection against the challenge of heterologous genotype GIII strains, showing a reduced protective efficacy of a GI-derived vaccine against GIII strain challenge. Overall, these observations demonstrated a partial cross-protection between GI and GIII strains and suggested a potential need for new JE vaccine strategies, including options like a bivalent vaccine, to control both genotype infection.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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Partial cross-protection between Japanese encephalitis virus genotype I and III in mice

et al. 2019

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“…Immunization of mice with the mutant VLP elicited similar immunogenicity and protection to those with the native cleavage site. Similar immunogenicity/protection in mice and pigs was respectively observed when plasmids encoding JEV prME genes were stably expressed in rabbit kidney-derived RK13 and CHO cells [40,41]. Following the above discoveries, several other groups also expressed plasmid vectors encoding JEV prME genes to produce JEV VLPs in different mammalian cells, yielding similar immunogenicity/protection in mice [42,43].…”

Section: Japanese Encephalitis Virusmentioning

confidence: 74%

Virus-Like Particle Systems for Vaccine Development against Viruses in the Flaviviridae Family

et al. 2019

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Viruses in the Flaviviridae family are important human and animal pathogens that impose serious threats to global public health. This family of viruses includes emerging and re-emerging viruses, most of which are transmitted by infected mosquito or tick bites. Currently, there is no protective vaccine or effective antiviral treatment against the majority of these viruses, and due to their growing spread, several strategies have been employed to manufacture prophylactic vaccines against these infectious agents including virus-like particle (VLP) subunit vaccines. VLPs are genomeless viral particles that resemble authentic viruses and contain critical repetitive conformational structures on their surface that can trigger the induction of both humoral and cellular responses, making them safe and ideal vaccine candidates against these viruses. In this review, we focus on the potential of the VLP platform in the current vaccine development against the medically important viruses in the Flaviviridae family.

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“…However, the expression of toxic E glycoproteins could limit the generation of stable cell lines capable of producing higher yields of VLPs in mammalian cells [24][25][26]. Nonetheless, JEV GI VLPs produced from stable mammalian cell lines have been shown to induce immunity against GI and GIII JEV in mice and swine [27]. The conventional baculovirus expression system has been employed to produce large quantities of JEV VLPs in insect cells [28,29]; however, the antigenicity of Lepidoptera-derived JEV VLPs has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Mosquito Cell-Derived Japanese Encephalitis Virus-Like Particles Induce Specific Humoral and Cellular Immune Responses in Mice

Chang

Chiao

Hsu

et al. 2020

Viruses

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The Japanese encephalitis virus (JEV) is the major cause of an acute encephalitis syndrome in many Asian countries, despite the fact that an effective vaccine has been developed. Virus-like particles (VLPs) are self-assembled multi-subunit protein structures which possess specific epitope antigenicities related to corresponding native viruses. These properties mean that VLPs are considered safe antigens that can be used in clinical applications. In this study, we developed a novel baculovirus/mosquito (BacMos) expression system which potentially enables the scalable production of JEV genotype III (GIII) VLPs (which are secreted from mosquito cells). The mosquito-cell-derived JEV VLPs comprised 30-nm spherical particles as well as precursor membrane protein (prM) and envelope (E) proteins with densities that ranged from 30% to 55% across a sucrose gradient. We used IgM antibody-capture enzyme-linked immunosorbent assays to assess the resemblance between VLPs and authentic virions and thereby characterized the epitope specific antigenicity of VLPs. VLP immunization was found to elicit a specific immune response toward a balanced IgG2a/IgG1 ratio. This response effectively neutralized both JEV GI and GIII and elicited a mixed Th1/Th2 response in mice. This study supports the development of mosquito cell-derived JEV VLPs to serve as candidate vaccines against JEV.

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Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine

Cited by 17 publications

References 58 publications

Partial cross-protection between Japanese encephalitis virus genotype I and III in mice

Partial cross-protection between Japanese encephalitis virus genotype I and III in mice

Virus-Like Particle Systems for Vaccine Development against Viruses in the Flaviviridae Family

Mosquito Cell-Derived Japanese Encephalitis Virus-Like Particles Induce Specific Humoral and Cellular Immune Responses in Mice

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